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- Title
Glutathione Depletion Increases Tyrosinase Activity in Human Melanoma Cells.
- Authors
del Marmol, Véronique; Solano, Francisco; Sels, André; Huez, Georges; Libert, Anita; Lejeune, Ferdinand; Ghanem, Ghanem
- Abstract
The aim of the present work was to estimate the effect of intracellular glutathione depletion on melanogenesis in human melanoma cells. We determined tyrosine hydroxylation activity, the rate-limiting step of the pathway, and 14C-melanin formation, an assay reflecting the global eumelanogenic pathway. Intracellular glutathione was depleted by treatment with buthionine-S-sulfoximine, a well-known inhibitor of γ-glutamylcysteine synthetase. The intracellular depletion of glutathione was substantial after 20 h of incubation with 50 μM buthionine-S-sulfoximine, although a significant effect could be observed after 6 h. Tyrosine hydroxylase activity increased in parallel with glutathione depletion, to reach 160% with respect to the control values during 24 h of buthionine-S-sulfoximine treatment. We have found the response to buthionine-S-sulfoximine to be dose dependent and the two different human cell lines HBL and LND1 to have similar, if not identical, responses. 14C-melanin formation assay revealed even greater activation, up to 400% of the control values. This indicates that glutathione depletion may have two distinct effects: first, a direct one on tyrosinase activity and, second, an effect on the promotion of eumelanogenesis. The stimulation of tyrosine hydroxylase can be explained by a possible inactivation of the enzyme by endogenous thiol compounds rather than by a direct effect of buthionine-S-sulfoximine itself on tyrosinase. The data suggest that thiol compounds may play a role for stimulation of melanogenesis by ultraviolet radiation.
- Subjects
MOLECULAR immunology; GLUTATHIONE; PHENOL oxidase; ENZYME kinetics; MELANOMA; CANCER cells; MELANOGENESIS; ULTRAVIOLET radiation
- Publication
Journal of Investigative Dermatology, 1993, Vol 101, Issue 6, p871
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12371709